Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity.
Extensive growth in the field of molecular biology in recent decades has led to the development of new and powerful experimental and computational tools that enable the analysis of complex biological responses to chemical exposure on both a functional and structural genetic level. The ability to profile global responses on a transcriptional level has become a valuable resource in the science of toxicology and attempts are now being made to further understand toxicity mechanisms by incorporating metabolomics and proteomics approaches. In addition, recent progress in understanding the extent of the genetic diversity within and between species allows us to take a fresh look at research on genetic polymorphisms that may influence an individual's susceptibility to toxicity. Whereas new technologies have the potential to make a sizeable impact on our understanding of the mechanisms of toxicity, considerable challenges remain to be addressed, especially with regard to the regulatory acceptance and successful integration of omics data. This review highlights recent advancements in the application of functional and structural genomics techniques to chemical hazard identification and characterization, and to the understanding of the interindividual differences in susceptibility to adverse drug reactions.
Harrill
Alison Hege
AH
University of North Carolina at Chapel Hill, 0031 Michael Hooker Research Center, Curriculum in Toxicology, CB 7431, Chapel Hill, NC, 27599, USA. iir@unc.edu
Rusyn
Ivan
I
D000818:Animals; D001709:Biotechnology; D064420:Drug-Related Side Effects and Adverse Reactions; D020869:Gene Expression Profiling; D006801:Humans; D049490:Systems Biology; D043922:Toxicogenetics